Faculty of Pharmacy, Department of Medicinal Chemistry, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Arch Pharm (Weinheim). 2018 Oct;351(10):e1800115. doi: 10.1002/ardp.201800115.
A novel series of cinnamic acid-tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid-tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC value of 0.55 ± 0.04 μM. This compound showed a 14-fold higher inhibitory potency than the standard drug donepezil (IC = 7.79 ± 0.81 μM) and inhibited BChE through a mixed-type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β-secretase, which exhibited low activity (inhibition percentage: 38%).
设计、合成了一系列新型肉桂酸-色胺杂合体，并将其作为胆碱酯酶抑制剂进行了评价。抗胆碱酯酶测定表明，所有合成的化合物均对丁酰胆碱酯酶（BChE）表现出明显的选择性抑制作用，但仅检测到对乙酰胆碱酯酶（AChE）的中度抑制作用。在这些肉桂酸-色胺杂合体中，化合物 7d 被发现是 BChE 的最强抑制剂，IC 值为 0.55±0.04μM。该化合物的抑制活性比标准药物多奈哌齐（IC50=7.79±0.81μM）高 14 倍，通过混合型抑制模式抑制 BChE。此外，对接研究表明，化合物 7d 结合到 BChE 的催化阴离子结合位点（CAS）和外周阴离子结合位点（PAS）。此外，还评估了化合物 7d 对β-分泌酶的活性，结果显示其活性较低（抑制率：38%）。
